Impact of Cytochromes P450 3A4 and 2B6 gene polymorphisms on predisposition and prognosis of acute myeloid leukemia: an Egyptian case-control study
Abstract Background It has been postulated that the interaction between environmental risk factors and genetic susceptibility is a possible cause for the development of acute myeloid leukemia (AML). Cytochrome P450 (CYP) detoxification enzymes are responsible for the elimination of oxidative stress....
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| Format: | Article |
| Language: | English |
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SpringerOpen
2021-04-01
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| Series: | Egyptian Journal of Medical Human Genetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s43042-021-00145-0 |
| _version_ | 1819142136995512320 |
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| author | Shahira Kamal Anis Botros Nesrine El Gharbawi Gehan Shahin Hend Al Lithy Mahmoud El Sherbiny |
| author_facet | Shahira Kamal Anis Botros Nesrine El Gharbawi Gehan Shahin Hend Al Lithy Mahmoud El Sherbiny |
| author_sort | Shahira Kamal Anis Botros |
| collection | DOAJ |
| description | Abstract Background It has been postulated that the interaction between environmental risk factors and genetic susceptibility is a possible cause for the development of acute myeloid leukemia (AML). Cytochrome P450 (CYP) detoxification enzymes are responsible for the elimination of oxidative stress. Genetic polymorphisms in these enzymes may cause AML due to enhanced accumulation of reactive oxygen species. To study the association between CYP3A4 (A290G) and CYP2B6 (G516T) gene polymorphisms and the predisposition and prognosis of AML, 50 upfront AML patients and 50 healthy individuals were genotyped for CYP2B6 (G516T) and CYP3A4 (A290G) single-nucleotide polymorphisms (SNPs) using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) technique. The polymorphisms were evaluated in relation to the response to chemotherapy and survival. Results CYP2B6 gene mutation carries a threefold risk of developing AML (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.3–6.9), whereas CYP3A4 gene mutation carries approximately fourfold risk (OR, 3.8; 95% CI, 1.4–10.1). The presence of combined gene mutation conferred about 15-fold increased risk of developing AML compared with the presence of a single gene mutation (OR, 14.8; 95% CI, 1.8–124.2). CYP3A4 gene mutation is associated with worse overall survival (P = 0.030). Conclusion CYP enzyme gene polymorphisms are associated with the development of AML. Elimination of oxidative stress in genetically susceptible individuals may decrease the risk of AML and may improve survival. |
| first_indexed | 2024-12-22T12:05:33Z |
| format | Article |
| id | doaj.art-a471963a6c1148fa893b940cf2e8092e |
| institution | Directory Open Access Journal |
| issn | 2090-2441 |
| language | English |
| last_indexed | 2024-12-22T12:05:33Z |
| publishDate | 2021-04-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj.art-a471963a6c1148fa893b940cf2e8092e2022-12-21T18:26:27ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412021-04-0122111010.1186/s43042-021-00145-0Impact of Cytochromes P450 3A4 and 2B6 gene polymorphisms on predisposition and prognosis of acute myeloid leukemia: an Egyptian case-control studyShahira Kamal Anis Botros0Nesrine El Gharbawi1Gehan Shahin2Hend Al Lithy3Mahmoud El Sherbiny4Clinical Pathology, Kasr Al Ainy Medical SchoolClinical Pathology, Kasr Al Ainy Medical SchoolClinical Pathology, Kasr Al Ainy Medical SchoolInternal Medicine, Kasr Al Ainy medical SchoolNasser Institute for Research and TreatmentAbstract Background It has been postulated that the interaction between environmental risk factors and genetic susceptibility is a possible cause for the development of acute myeloid leukemia (AML). Cytochrome P450 (CYP) detoxification enzymes are responsible for the elimination of oxidative stress. Genetic polymorphisms in these enzymes may cause AML due to enhanced accumulation of reactive oxygen species. To study the association between CYP3A4 (A290G) and CYP2B6 (G516T) gene polymorphisms and the predisposition and prognosis of AML, 50 upfront AML patients and 50 healthy individuals were genotyped for CYP2B6 (G516T) and CYP3A4 (A290G) single-nucleotide polymorphisms (SNPs) using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) technique. The polymorphisms were evaluated in relation to the response to chemotherapy and survival. Results CYP2B6 gene mutation carries a threefold risk of developing AML (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.3–6.9), whereas CYP3A4 gene mutation carries approximately fourfold risk (OR, 3.8; 95% CI, 1.4–10.1). The presence of combined gene mutation conferred about 15-fold increased risk of developing AML compared with the presence of a single gene mutation (OR, 14.8; 95% CI, 1.8–124.2). CYP3A4 gene mutation is associated with worse overall survival (P = 0.030). Conclusion CYP enzyme gene polymorphisms are associated with the development of AML. Elimination of oxidative stress in genetically susceptible individuals may decrease the risk of AML and may improve survival.https://doi.org/10.1186/s43042-021-00145-0AMLCYPGene polymorphism |
| spellingShingle | Shahira Kamal Anis Botros Nesrine El Gharbawi Gehan Shahin Hend Al Lithy Mahmoud El Sherbiny Impact of Cytochromes P450 3A4 and 2B6 gene polymorphisms on predisposition and prognosis of acute myeloid leukemia: an Egyptian case-control study Egyptian Journal of Medical Human Genetics AML CYP Gene polymorphism |
| title | Impact of Cytochromes P450 3A4 and 2B6 gene polymorphisms on predisposition and prognosis of acute myeloid leukemia: an Egyptian case-control study |
| title_full | Impact of Cytochromes P450 3A4 and 2B6 gene polymorphisms on predisposition and prognosis of acute myeloid leukemia: an Egyptian case-control study |
| title_fullStr | Impact of Cytochromes P450 3A4 and 2B6 gene polymorphisms on predisposition and prognosis of acute myeloid leukemia: an Egyptian case-control study |
| title_full_unstemmed | Impact of Cytochromes P450 3A4 and 2B6 gene polymorphisms on predisposition and prognosis of acute myeloid leukemia: an Egyptian case-control study |
| title_short | Impact of Cytochromes P450 3A4 and 2B6 gene polymorphisms on predisposition and prognosis of acute myeloid leukemia: an Egyptian case-control study |
| title_sort | impact of cytochromes p450 3a4 and 2b6 gene polymorphisms on predisposition and prognosis of acute myeloid leukemia an egyptian case control study |
| topic | AML CYP Gene polymorphism |
| url | https://doi.org/10.1186/s43042-021-00145-0 |
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